evaluation of the gastrointestinal manifestation of fabry's disease

Conditions: Fabry's Disease

Summary: patients will undergo a smartpill test to gain additional understanding of fabry disease manifestation via motility abnormalities in order to improve symptom targeted therapy. an additional endoscopic mucosal resection may be performed on further qualifying patients. tissue analysis from this biopsy will include evaluation of abnormalities of cellular structure and morphology with correlation with gastrointestinal complaints for each patient and comparison against age matched non-fabry patient tissue. the hypothesis is that patients with fabry disease will have abnormal motility which will correlate with the patients symptoms and quality of life as noted on the questionnaires.

background: gastrointestinal manifestations such as abdominal pain, diarrhea and nausea are prominent and, although typically non life-threatening, can frequently cause significant morbidity and burden in a patient with fabry disease. additional in depth understanding of gastrointestinal symptoms pathophysiology in fabry disease is acutely needed in order to develop more specific evaluation of the symptoms and advance the treatment of these patients. hypothesis: patients with gastrointestinal (gi) symptoms will have delayed motility on the smartpill study, abnormal histologic findings on mucosal resection and symptoms that correlate with abnormal histologic and smartpill findings. by gaining additional insight into the characterization of symptoms and the relationship to dysmotility, we anticipate improved and more focused adjunct therapies for the patients. methods: this study will consist of a screening visit, a smartpill testing procedure visit, and a follow up visit for all subjects enrolled in the study. fifteen of these patients, who clinically warranted sigmoidoscopy, will be asked to also complete an endoscopic mucosal resection (emr) visit in addition to the other aspects of the study. thus, each subject will report to the study site for at least 3 visits and up to 4 visits.

Eligibility criteria:
inclusion criteria: * adults ages 18-70 years who have diagnosed fabry disease either by enzyme testing in males or by enzyme and/or genetically confirmed mutation in females. * adults with fabry disease having any gastrointestinal complaints within the past year. * endoscopic mucosal resection only - symptomatic subjects necessitating a sigmoidoscopy who are enzyme replacement therapy (ert) naive or less than 6 months of treatment. exclusion criteria: 1. fabry disease with other concomitant gastrointestinal diagnosis (example: inflammatory bowel disease, celiac disease) 2. pregnancy 3. endoscopic mucosal resection exclusions: 1. any contraindication to conscious sedation, 2. contraindication to endoscopy, 3. untreated or unmanageable coagulopathy, 4. thrombocytopenia (\<50). 5. patient on ert for more than 6 months. 4. exclusions for smartpill: 1. previous history of bezoars. 2. prior gi surgery except for cholecystectomy, appendectomy, or nissen fundoplication. 3. any abdominal surgery within the past 3 months 4. history of diverticulitis, diverticular stricture, and other intestinal strictures 5. tobacco use within eight hours prior to capsule ingestion and during the initial 8-hour recording on day 0 or the ingestion visit. 6. alcohol use within eight hours prior to capsule ingestion and throughout the entire monitoring period (5 days). 7. bmi \> 38 8. allergies to components of the smartbar 9. use of medical devices such as pacemakers, infusion pumps, or insulin pumps. 10. uncontrolled diabetes with a hemoglobin a1c greater than 10.

Keywords: fabry's disease fabry